tbuckley/cabot-search huggingface dataset:
The profile study: Prostate cancer screening in men of Black African and African Caribbean ancestry—Early results.
Authors: Netty Kinsella, Jana Kathlyn McHugh, Eva McGrowder, Denzil James, Ed Saunders, Elizabeth Bancroft, Zsofia Kote-Jarai, Ros A. Eeles
Journal: Journal of Clinical Oncology (2023)

306 Background: Heritable risk factors account for a significant proportion of prostate cancer (PrCa) risk, of which only a minority are high risk Mendelian traits. Men of Black African and African Caribbean ancestry are at higher risk of developing PrCa in their lifetime (1 in 4) compared with the general population in the United Kingdom (1 in 8). PROFILE is a multi-cohort study of targeted screening for groups of men at higher risk of developing PrCa: 1) men of European ancestry with family history of PrCa, 2) men of black African and African Caribbean ancestry regardless of family history and 3) men with known rarer higher risk gene mutations for PrCa. This abstract concentrates on group 2. The aim is to investigate the role of targeted PrCa screening in men at higher genetic risk and its association with specific genetic profiles and biomarkers. Methods: Healthy men aged 40-69 are invited to participate. Inclusion Criteria: Both parents and all four grandparents must be of either black African or African Caribbean ancestry. Arm 1: PSA only – once PSA is below an age-related threshold (aged 40-49 and PSA ≥0ng/ml, aged 50-69 PSA &gt;/= 2ng/ml) they continue on the study with annual PSA, only triggering a prostate MRI and Biopsy if the PSA is above the threshold. Arm 2: Regardless of PSA men opt for prostate mpMRI and biopsy. Polygenic risk score (PRS) calculated based on 230 SNPs including latest AA specific variants. Results: Arm 1: 121 enrolled PSA only (this has triggered 8 biopsies with 3 cancers). Arm 2: 58 enrolled MRI and biopsy, 58 MRIs and 36 biopsies carried out, PrCa detected in 15 men (42%). 22% are Gleason score ≥7. Association between PRS and MRI/Biopsy results will be presented. Conclusions: We will continue to perform MRI and biopsies on men, we will also carry out polygenic risk scores on these men to verify whether a genetic PRS can help guide enhanced screening for certain men in the population. Although data are early, a significant proportion of biopsies are positive for PrCa that needs radical treatment. Clinical trial information: NCT02543905 .
Impact of age on the therapy-related characteristics and outcomes of testicular germ cell tumors at a tertiary care center in India.
Authors: Neha Pathak, Sudhir Kumar, Abhishek Raj, Ranjit Kumar Sahoo, Haresh KP, Prabhjot Singh, Shamim Ahmed Shamim, Amlesh Seth, M D Ray, Seema Kaushal, Chandan Krushna Das, Atul Batra
Journal: Journal of Clinical Oncology (2023)

415 Background: Testicular germ cell tumors (t-GCTs) commonly present in age group 20-40 years (yrs). Older patients (pts) in many cancers have worse tolerance to therapy and outcomes. We examine herein the effect of older age in t-GCT pts. Methods: We conducted a chart-review-based retrospective analysis of pts of t-GCTs diagnosed and treated at our urogenital clinic from 2015-2021. Pts were divided into two groups: Age ≤40 years (Group A) and &gt;40 years (Group B). Multivariable Cox regression models were constructed to analyze the prognostic value of older age while adjusting for measured confounders. Results: A total of 298 patients of t-GCT were identified; the median age was 30 yrs (interquartile range 24-37), 43.0% with intermediate or poor risk, 64.8% patients with non-seminomatous GCT (NSGCT), 250 pts in gp A and 48 in gp B. Baseline characteristics in both gps differed significantly with respect to the risk category, and seminoma histology, while there was no difference for performance status (ECOG ≥2), see table. Bleomycin, cisplatin, and etoposide (BEP) was the most common chemotherapy (226/262 pts), and use of BEP was not different in 2 gps (p=0.249). Grade III/IV adverse effect burden was greater in gp B vs gp A for febrile neutropenia, nausea/vomiting, and diarrhea, while infertility was more in gp A (Table). Outcomes in terms of markers normalization (163 vs 33, p=0.408) and radiological response (complete remission, 93 vs 20, p=0.205) did not differ. Median overall survival was not reached in both gps, and the hazard ratio for age &gt;40 yrs was 1.91 (95% confidence interval 0.91-3.99, p =0.086), after adjusting for risk category, performance status, and response to therapy. Conclusions: Age does not deter the use of platinum-based therapy, which, although more toxic, has similar efficacy to younger pts of t-GCT. [Table: see text]
Optimising bone health management in advanced prostate cancer: A comparative cohort study.
Authors: Anthony Waton, Rachel Prichard, Carolina Navarro Rodriquez, Nicola Hannaway, Ashraf Azzabi, Robert Chandler, John A. Frew, Xue Yan Jiang, Rachel Pearson, Ian Pedley
Journal: Journal of Clinical Oncology (2023)

133 Background: Survival in prostate cancer is increasing due to advances in hormonal therapy. The recommended duration of Androgen Deprivation Therapy (ADT) is 18 months or more for patients with Non-Metastatic (NM) high risk disease, and lifelong in Metastatic disease. ADT is, however, an independent risk factor for osteoporosis, a disease characterised by low Bone Mineral Density (BMD) and subsequent increased risk of fractures, which can lead to significant disability and early death. In patients with advanced prostate cancer, it is therefore recommended that BMD is assessed yet there remains no established national guidance on how bone health should be managed. Methods: In total, 515 case notes for patients with newly diagnosed advanced hormone sensitive prostate cancer were retrospectively reviewed for assessment of bone health management. Our data analysis included a comparison of outcomes between patient cohorts managed at a dedicated Cancer Bone Health Unit (CBHU) and the Northern centre for Cancer Care (Oncology Centre, OC). Results: 1) Baseline characteristics: The cohorts were well balanced in terms of age and cancer stage. Data was available for 410 patients in the CBHU and 105 in the OC. Median age was 75 (range 59-94) in the CBHU and 71 (range 46-86) in the OC. The majority of patients had metastatic disease and were therefore receiving lifelong ADT. 2) Fracture incidence: was consistently higher in the OC (p&lt;0.001). The most common fractures were hip, spine and wrist. Median time to first fracture in the CBHU was 112 (range 2 to 240) vs 83 weeks (8 to 229) in the OC (p=0.252). 3) Survival: for all patients 2 years after ADT commenced was 96.7% in the CBHU vs 91.8% in the OC (HR 0.321, 95% CI 0.19-0.55, p&lt;0.001). Median survival has not yet been reached. Conclusions: This comparative analysis suggests that a strategy of standardised bone health management within a CBHU is associated with reduced fracture incidence and may delay time to first fracture compared with clinician discretion in an OC. Additionally the data suggests that this strategy also improves survival at 2 years in patients with NM high risk disease. Bone health strategies for prostate cancer should be implemented within hospital trusts to provide standardised care across the region. This could reduce costs associated with fractures and improve quality of life for patients who avoid fractures through timely introduction of treatment. The Northern Cancer Alliance (NCA) has recently approved guidance on the management of bone health in prostate cancer, and implementation has since commenced.
Characterizing changes in tumor mutational burden (TMB) by serial circulating tumor DNA (ctDNA) testing in patients with advanced prostate cancer (aPC).
Authors: Daniel S Childs, Eugene D. Kwon, Mohamed E. Ahmed, Ahmed Mahmoud, Rodrigo Rodrigues Pessoa, Reza Nabavizadeh, Jill Tsai, Leylah Drusbosky, Leslie Bucheit
Journal: Journal of Clinical Oncology (2023)

239 Background: In part, TMB guides therapeutic decisions on the use of immune checkpoint inhibitors (ICIs) in aPC. Most patients (pts) with aPC do not have high TMB (TMB-H) at the time of initial assessment. However, TMB changes over time (from treatment pressure) as pts progress through lines of therapy (LOT) has not been extensively explored in aPC. We describe real world data on changes to blood TMB (bTMB) in pts with aPC exposed to several LOT. Methods: Genomic results from pts with aPC who had ≥1 ctDNA test(s) with TMB analyzed (Guardant360, Guardant Health, Inc) as part of clinical care from Oct 2020 – Jun 2022 were retrospectively queried. Clinical factors were extracted from test requisition forms; pts from Mayo Clinic had additional factors, including intervening treatment, extracted from medical records. High bTMB (TMB-H) was defined as ≥13.4 mut/Mb, as previously reported. Proportions were compared using Fisher’s Exact Test. Results: 316 patients with a median age of 72 (range: 44-91) were analyzed. Initial median TMB for the entire cohort was 8.18 mut/Mb (range: 0.01-268.3). On subsequent test, TMB decreased in 122(40%), increased in 173(55%), of whom 29 (17%) became TMB-H; 21 (7%) had unchanged TMB. Median time between tests was 182 days (range: 21-578). 101 patients with 262 tests and a median age of 71 years (range: 46-87) were clinically annotated in the Mayo cohort of whom 58 had &gt;2 consecutive TMB scores: 25 (43%) had TMB increase, of whom 4 (16%) became TMB-H, 23 (40%) had TMB decrease, 10 (17%) had dynamic changes with increases and decreases. Numeric but not statistically significant differences in clinical factors were observed between groups (p&gt;0.05). Conclusions: In this real world cohort, variation in TMB is seen with increasing LOT. Importantly, nearly 1 in 5 patients with increasing tumor mutational burden develop TMB-H, which may be a clinically actionable finding as these pts become eligible for ICI. Findings underscore the importance of repeat genetic testing with time and LOT. [Table: see text]
Trends in the use of local intervention and its impact on oncological outcomes for metastatic castration-sensitive prostate cancer: A multicenter retrospective study.
Authors: Shingo Hatakeyama, Shintaro Narita, Toshikazu Tanaka, Toshihiko Sakurai, Akihiro Ito, Norihiko Tsuchiya, Tomonori Habuchi, Chikara Ohyama
Journal: Journal of Clinical Oncology (2023)

354 Background: The role of local intervention in addition to the standard of care for metastatic castration-sensitive prostate cancer (mCSPC) is unknown. Therefore, this study evaluated the trends of local intervention and their impact on oncological outcomes in patients with mCSPC in real-world practice. Methods: This multicenter retrospective study included 760 patients treated with either androgen deprivation therapy (ADT) without local treatment (no castration-resistant prostate cancer [CRPC] progression within 12 months, control group) or ADT plus local intervention (intervention group) between January 2005 and March 2022. The primary outcome was trends in the use of local intervention in patients with mCSPC. The secondary outcomes included evaluations of factors associated with CRPC-free survival in the intervention group. Results: The use of local intervention gradually increased in combination with upfront treatment for the duration of our study. The number of patients with local intervention combined with upfront treatment was significantly higher in patients with high tumor burden disease than in those with low tumor burden disease. Of the 108 patients who received local intervention comprising radiation therapy targeted to the prostate, a duration of &gt;7 months of initial therapy before local intervention and a level of prostate-specific antigen &lt;0.20 ng/mL at the time of local intervention were significantly associated with prolonged CRPC-free survival. Conclusions: Regardless of the tumor burden, the use of local intervention in combination with upfront therapy to treat mCSPC increased for the duration of our study. Local intervention in addition to the standard of care for mCSPC may be a feasible treatment option for selected patients, taking into consideration the duration of and response to initial treatment.
Niraparib (NIRA) with abiraterone acetate and prednisone (AAP) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: Second interim analysis (IA2) of MAGNITUDE.
Authors: Eleni Efstathiou, Matthew Raymond Smith, Shahneen Sandhu, Gerhardt Attard, Marniza Saad, David Olmos, Elena Castro, Guilhem Roubaud, Andrea Juliana Gomes, Eric Jay Small, Dana E. Rathkopf, Howard Gurney, Wonho Jung, Gary Mason, Peter St. John Francis, George C. Wang, Daphne Wu, Brooke Diorio, Angela Mennicke Lopez- Gitlitz, Kim N. Chi
Journal: Journal of Clinical Oncology (2023)

170 Background: In the primary analysis of the phase 3 MAGNITUDE study, NIRA/AAP significantly improved outcomes in pts with mCRPC and HRR gene alterations. Here, we report results from IA2 of secondary endpoints in MAGNITUDE. Methods: 423 eligible pts with mCRPC and HRR alterations (HRR+ cohort) were randomized 1:1 to receive NIRA/AAP (n = 212) or placebo (PBO)/AAP (n = 211). At the prespecified IA2, secondary endpoints (time to cytotoxic chemotherapy [TCC], time to symptomatic progression [TSP], overall survival [OS]) were formally assessed and the primary rPFS endpoint was updated in the HRR+ cohort, with sensitivity analysis performed for the subgroup of pts with BRCA alterations. Results: Updated descriptive rPFS results at IA2 (cutoff: June 17, 2022) were consistent with the primary analysis in the HRR+ cohort. In the BRCA subgroup, NIRA/AAP extended median rPFS to 19.5 mos vs 10.9 mos with PBO/AAP. NIRA/AAP led to statistically significant benefit in TSP in the HRR+ cohort with consistent benefit in the BRCA subgroup. Continued consistent improvement of TCC was seen with NIRA/AAP in the HRR+ cohort and in the BRCA subgroup. There was a trend towards improved OS with NIRA/AAP in the BRCA subgroup in the primary stratified analysis and the multivariate analysis (MVA), accounting for imbalances in key baseline characteristics. BRCA pts treated with NIRA/AAP experienced delayed time to worst pain intensity (HR, 0.70; 95% CI, 0.44, 1.12; nominal P = 0.1338) and pain interference (HR, 0.67; 95% CI, 0.40, 1.12; nominal P = 0.1275) compared to PBO/AAP. The safety profile at IA2 was consistent with that of the primary analysis, with no new safety signals observed. Conclusions: With 26.8 months of median follow-up, there was a statistically significant and meaningful clinical benefit in TSP and meaningful clinical benefit in TCC. Additionally, updated rPFS results from MAGNITUDE IA2 were consistent with the primary analysis; OS benefit was not conclusive due to immaturity and will be followed through to final analysis. Taken together, these data continue to support the use of NIRA/AAP in pts with mCRPC and BRCA alterations or select other HRR gene alterations. Clinical trial information: NCT03748641 . [Table: see text]
The survival benefit of metastasectomy for metastatic non-clear cell renal cell carcinoma.
Authors: Jindong Dai, Xu Hu, Haoran Zhang, Yaowen Zhang, Xingming Zhang, Guangxi Sun, Hao Zeng, Pengfei Shen, Zhenhua Liu
Journal: Journal of Clinical Oncology (2023)

686 Background: A subset of patients with metastatic clear cell renal cell carcinoma (ccRCC) might benefit from metastasectomy, while those with metastatic non-clear cell carcinoma (non-ccRCC) might be potential candidates for metastasectomy remains unclear. Methods: From the metastatic RCC database of West China Hospital, a total of 114 patients with confirmed metastatic non-ccRCC were identified. Patients were divided into groups by systemic therapy plus nephrectomy and metastasectomy or systemic therapy plus nephrectomy alone. Clinical outcomes included overall survival (OS) and progression-free survival (PFS). The potential factors predicting clinical benefits from cytoreductive surgery (including nephrectomy and metastasectomy) were also explored using Cox regression and Kaplan-Meier analyses. Results: 100 patients received nephrectomy alone and another 14 patients who underwent nephrectomy and metastasectomy were enrolled in the present study. In addition, total of 19 metastatic lesions were dissected among 14 patients. Compare to patients with systemic therapy plus nephrectomy alone, systemic therapy plus nephrectomy and metastasectomy could significantly improve the progression-free survival (PFS) (27.1 vs. 12.4 months, HR: 0.352, 95%CI: 0.108-1.143, p=0.046). For patients with synchronous metastasis, only systemic therapy plus nephrectomy alone showed an advantage in the PFS (HR: 0.363, 95%CI: 0.179-0.737, P=0.005) and OS (HR: 0.172, 95%CI: 0.080-0.371, P&lt;0.001). And for patients with metachronous metastasis, systemic therapy plus nephrectomy and metastasectomy could improve the PFS (HR: 0.124, 95%CI: 0.016-0.956, P=0.045) and OS (HR: 0.250, 95%CI: 0.059-0.971, P=0.043). None of the patients had any serious (Clavien-Dindo Classification ≥III grade) perioperative complications. Conclusions: Metastasectomy could be one of the optional treatments for patients with metastatic non-ccRCC. For patients with synchronous metastases, only nephrectomy could improve prognosis; however, patients with metachronous metastases might get benefit from metastasectomy.
Associations between plant-based diets and risk of disease progression in men with prostate cancer.
Authors: Vivian N Liu, Erin L. Van Blarigan, Li Zhang, Rebecca E. Graff, Crystal Langlais, Janet E. Cowan, Peter Carroll, June M. Chan, Stacey A. Kenfield
Journal: Journal of Clinical Oncology (2023)

392 Background: Plant-based diets have been linked to multiple health benefits. For prostate cancer (PC), individual plant foods (e.g., tomatoes with lycopene) appear to reduce PC incidence and mortality. However, less is known about plant-based dietary patterns and PC survivorship. Methods: We examined 2038 men diagnosed with T1-T3a PC who were enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) and had completed a food frequency questionnaire (FFQ) a median of 31.5 months post-diagnosis. “Overall” and “healthy plant-based” dietary indices (PDI and hPDI, respectively,) were calculated from the FFQ. Multivariable Cox proportional hazards models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between plant-based diets and risk of PC progression (recurrence, secondary treatment, bone metastases, or PC death) as the primary outcome, and PC recurrence as a secondary outcome. We also examined whether age, stage, grade, and walking pace modified associations. Results: We observed 204 progression events (169 due to biochemical recurrence) over a median follow up of 7.4 years after the FFQ. Men in the highest quintile of PDI had a 52% lower risk of progression (HR 0.48, 95% CI 0.36-0.65, p-trend&lt;0.001) and a 53% lower risk of recurrence (HR 0.47, 95% CI 0.32-0.68, p-trend&lt;0.001) compared to men in the lowest quintile. Although the hPDI was not associated with PC progression or recurrence overall (p-trend &gt;0.05), men in the higher quintiles had statistically significant reductions in risk of recurrence. Among men &gt;65 years, greater consumption of a healthful plant-based diet was associated with lower risk of PC recurrence (HR 0.41, 95% CI 0.24-0.7, p-trend=0.03). In addition, among those with a brisk/fast walking pace (&gt;3 h/wk), men in the highest PDI quintile had a 56% (HR 0.33, 95% CI 0.26, 0.73) lower risk of PC progression, and a 59% (HR 0.41, 95% CI 0.25, 0.68) decrease in risk of PC recurrence. Grade and stage did not modify associations between either index and PC progression or recurrence. Conclusions: This study indicates that plant-based dietary patterns are associated with lower risk of PC progression and recurrence, particularly among older men and those who reported a higher intensity walking pace. PC survivors may be recommended diet and exercise counseling to improve clinical outcomes after PC diagnosis.
Comparative real-world survival outcomes of muscle-invasive bladder cancer treated with bladder-only vs. whole-pelvis concurrent chemoradiation.
Authors: Carlos Riveros, Sanjana Ranganathan, Waqar Haque, Jiaqiong Xu, Michael Geng, Maryam Anis, Taliah Muhammad, Andrew M. Farach, Bin S. Teh, Christopher J.D. Wallis, Guru P. Sonpavde, Raj Satkunasivam
Journal: Journal of Clinical Oncology (2023)

488 Background: Elective nodal irradiation for patients with muscle-invasive bladder cancer (MIBC) undergoing trimodal therapy (TMT) is controversial. In patients with node-negative (N0) MIBC, the benefit of elective whole-pelvis concurrent chemoradiotherapy (WP-CCRT) compared to bladder-only (BO)-CCRT has not been demonstrated. Currently, the National Comprehensive Cancer Network (NCCN) guidelines do not recommend whether to include pelvic nodes in the radiation field. Using real-world data from the National Cancer Database (NCDB), we sought to compare the overall survival (OS) between BO-CCRT and WP-CCRT for MIBC. Methods: Using the 2019 NCDB Participant User File, we identified cases of MIBC diagnosed between 2017 and 2018. We selected patients with clinical T2-T4N0M0 disease receiving TMT as first-line treatment. TMT was defined as transurethral resection of bladder tumor followed by CCRT: 60–65 Gy of RT delivered to the bladder with concurrent single- or multiple-agent chemotherapy. Patients were stratified into BO-CCRT vs. WP-CCRT. Overall survival (OS) analysis was performed using Kaplan-Meier estimates and multivariable Cox proportional hazards regression analysis. The variables included in the multivariable Cox regression model were age, sex, race, comorbidity burden (as per the Charlson-Deyo comorbidity index), facility type, insurance status, median income quartile, rurality, distance from facility, and clinical T stage. Results: A total of 605 patients receiving TMT for MIBC were identified: 162 (26.8%) BO-CCRT and 443 (73.2%) WP-CCRT. The median follow-up time was 25.6 months (interquartile range [IQR]: 4.8-42.6) and 28.7 months (IQR: 3.0-51.6) for BO-CCRT and WP-CCRT, respectively. The median OS was 32.9 months (95% confidence interval [CI] 30.8 – not reached) and 48.3 months (95% CI 39.6 – not reached) for BO-CCRT and WP-CCRT, respectively. However, multivariable Cox regression analysis failed to find an association between WP-CCRT (hazard ratio [HR] 1.08, 95% CI 0.76-1.54) and improved OS, compared to BO-CCRT. Conclusions: Elective nodal-irradiation (WP-CCRT) in the setting of TMT for MIBC was not associated with a benefit in OS compared to BO-CCRT.